Alice Chandra Verticchio Vercellin

Structure/Function relationship and retinal ganglion cells counts to discriminate glaucomatous damages

BackgroundGlaucoma is an optic neuropathy characterized by retinal ganglion cells (RGC) loss and retinal nerve fiber layer (RNFL) injury: this results in functional and morphological changes. The first can be observed by Standard Automated Perimetry (SAP), the second by Optic Coherence Tomography (OCT) that measures the RNFL and ganglion cell complex (GCC) thicknesses. Nevertheless, diagnosis of early glaucoma may be difficult. Recently, Medeiros et al. derived an empirical formula combining the measurement of structural and functional tests to provide an estimate of RGC. The aim of the current study is to analyse the correlation between RGC count, estimated by Medeiros’ formula, and the structural and functional parameters in patients examined for glaucoma and to evaluate SAP, OCT and RGC counts capability to discriminate the weight of the disease itself.MethodsNinety four eyes of 50 consecutive patients clinically referring to glaucoma service of the Universitary Eye Clinic were submitted to a complete ophthalmic evaluation including SAP and Spectral Domain OCT (SD-OCT) of RNFL and macular GCC. Average thickness of RNFL and macular GCC, parameters Global Loss Volume (GLV) and Focal Loss Volume (FLV) over the entire GCC map were taken into account. Estimates of RGC were obtained with the help of a model already published by Medeiros et al. combining light sensitivities from SAP and retinal thickness from OCT. The RGC count was estimated in the entire visual field (central 24°) and in the GCC macular area and then compared with functional and morphological parameters applying Pearson’s correlation coefficient.ResultsAfter the classification of the patients by the Glaucoma Staging System 2 of Brusini, we noticed a good correlation among the functional parameters considered, even if the Visual Field Index is unable to identify early glaucoma. An analogous result can be observed for structural data (RNFL and GCC). The correlation detected between functional and structural parameters was moderate. Great differences in RGC counts were found between groups at various stages of glaucoma. GLV showed highest level of correlation (r > −0.8) with RCG counts.ConclusionsEstimate circumpapillary and macular RGC counts can discriminate various stages of the disease and there is also a good/very good correlation with both functional and structural parameters. GLV could be used instead of RGC counts in clinical practice.

Color Doppler Imaging and Glaucoma: Comparison of Doppler Waveform of Retrobulbar Vessels between a Glaucomatous Patient and a Healthy Subject

Ocular blood flow abnormalities are believed to play an important role in the pathogenesis of primary open angle glaucoma (POAG). For this reason the Color Doppler Imaging (CDI) evaluation of the retro bulbar vessels is used for research purposes to investigate the degree of these abnormalities and their role in the pathogenesis of PAOG. The most widely measured variables are peak systolic velocity (PSV), end-diastolic velocity (EDV) and resistivity index (RI) of the ophthalmic artery, central retinal artery, and short posterior ciliary arteries. According to a recent study that has found statistically significant differences in two variables measured in the ophthalmic artery, the early systolic acceleration (ESA) and the ratio between the mean velocities of the systolic and diastolic components (Sm/Dm), we present the CDI evaluation of a case of normal tension glaucoma (NTG) compared to a healthy subject. The values obtained are in agreement with the literature and all the measured velocities, except for the PSV and the RIs in the ophthalmic artery that were respectively reduced and increased as compared to the healthy volunteer. Moreover, ESA is reduced and Sm/Dm increased. Further studies are needed to evaluate the degree of the pathological alterations and their role in the progression of the optic nerve injury.

Cataracts and Dupuytren disease: a case report and review of the literature

Purpose. Dupuytren disease is an inherited proliferative and progressive connective disease. Ectopic disease may, however, be located distant from the palmar fascia. Methods. Case report and review of the literature. Results. We describe a case of symmetric bilateral posterior subcapsular cataracts associated with symmetric bilateral Dupuytren disease and symmetric bilateral Ledderhose disease in a 56-year-old Caucasian man. His medical history was negative for glucocorticoids intake, diabetes, and exposure to radiation. Serum transforming growth factor β (TGF-β)1 concentration has been evaluated and was found to be almost double compared to the controls. Conclusions. We speculate that the TGF-β plays an important role for ocular and connective tissue disorders.

Diagnostic Capability of Three-Dimensional Macular Parameters for Glaucoma Using Optical Coherence Tomography Volume Scans

Purpose To compare the diagnostic capability of three-dimensional (3D) macular parameters against traditional two-dimensional (2D) retinal nerve fiber layer (RNFL) thickness using spectral domain optical coherence tomography. To determine if manual correction and interpolation of B-scans improve the ability of 3D macular parameters to diagnose glaucoma. Methods A total of 101 open angle glaucoma patients (29 with early glaucoma) and 57 healthy subjects had peripapillary 2D RNFL thickness and 3D macular volume scans. Four parameters were calculated for six different-sized annuli: total macular thickness (M-thickness), total macular volume (M-volume), ganglion cell complex (GCC) thickness, and GCC volume of the innermost 3 macular layers (retinal nerve fiber layer + ganglion cell layer + inner plexiform layer). All macular parameters were calculated with and without correction and interpolation of frames with artifacts. The areas under the receiver operating characteristic curves (AUROC) were calculated for all the parameters. Results The 3D macular parameter with the best diagnostic performance was GCC-volume-34, with an inner diameter of 3 mm and an outer of 4 mm. The AUROC for RNFL thickness and GCC-volume-34 were statistically similar for all regions (global: RNFL thickness 0.956, GCC-volume-34 0.939, P value = 0.3827), except for the temporal GCC-volume-34, which was significantly better than temporal RNFL thickness (P value = 0.0067). Correction of artifacts did not significantly change the AUROC of macular parameters (P values between 0.8452 and 1.0000). Conclusions The diagnostic performance of best macular parameters (GCC-volume-34 and GCC-thickness-34) were similar to or better than 2D RNFL thickness. Manual correction of artifacts with data interpolation is unnecessary in the clinical setting.

Computer-aided ophthalmic artery waveform analysis in healthy individuals and glaucoma patients

We thank Michael Brodsky for his interest in our study and for drawing our attention to a paper by Brodsky and Klaehn that examined optokinetic responses in humans with infantile esotropia using what the authors labeled an ‘‘optokinetic uncover test.’’ We commend Brodsky and Klaehn on the observations and conclusions that they draw from their study. However, we would like to point out some key differences between their study and our study. A major difference is in the construction and delivery of the stimulus. Brodsky and Klaehn presented the patients with an optokinetic stimulus, first monocularly to the fixating eye and then binocularly. Further, the stimulus itself was full field, that is, not localized to any part of the visual field of the deviated eye. In our study, we utilized a dichoptic presentation in which the optokinetic stimulus is presented only to the deviated eye (never binocularly) and the fixating eye sees only a stationary target. Moreover, the optokinetic stimulation is restricted to a 108 patch, and we observed optokinetic nystagmus (OKN) only when the patch occupied the central 108 of the deviated eye that included the fovea. We also made quantitative evaluations of the strength of the OKN response and its gradation with spatial location and contrast of the OKN stimulus, whereas the Brodsky and Klaehn study was essentially a qualitative evaluation of the OKN response. Therefore, in our view, the two studies are not directly comparable. However, our results do agree with one of the conclusions that they reached, which was that information is being processed via both eyes. In his letter, Brodsky does not question our results but perhaps suggests two additional discussion points with regard to our study: (1) The OKN responses that we observed are driven by a subcortical optokinetic circuit, that is, no cortical involvement, and (2) cortical suppression of the fovea of the deviating eye might still have been present because the OKN leaked through via the subcortical pathway. In response to his two points, we make the following arguments. (1) In strabismus, nasotemporal asymmetry is observed in motion detection, visually evoked potential (VEP) response, smooth pursuit, and OKN. Neurophysiological investigation in strabismic monkeys has shown loss of binocularity in cortical areas V1, MT, MST, and also in brainstem area nucleus of the optic tract (NOT). Therefore, as proposed by models in the literature, the loss of binocular connections in the pathway from V1 MT MST NOT could lead to asymmetric visual or oculomotor response to monocular motion stimuli. Subcortical projections (direct retina–NOT projections) may also play a role, but it is not clear that they play an exclusive or primary role in generating nasalward OKN in strabismus. (2) Our study was focused on identifying areas of retinal suppression in strabismus, and OKN was simply used as a readout to identify suppressed versus unsuppressed retina. Our data and conclusions fit in nicely with the previous work in the literature. For instance, Economides, Adams, and Horton used a visual psychophysical paradigm, and showed that the fovea of the deviated eye was not suppressed. In addition, other work from our lab in which we used a saccade paradigm to examine spatial patterns of fixation switch behavior (presumably driven by suppression) also revealed similar results. Taken together with these other studies, our current study does indeed support the idea of lack of suppression of the fovea of the deviated eye in exotropia. Finally, we would like to point out that the discussion points above are fundamentally speculative because neither Brodsky’s previous work nor our current study directly examined neural responses, and therefore cannot ascribe the optokinetic responses to cortical/subcortical pathways. As always in science, the best way to settle the issue would be to design and perform an appropriate experiment and quantitatively evaluate the data.

Evaluation of the conjuntival blebs using spectral domain optical coherence tomography after glaucoma surgery

Objective: Analyze the application of the spectral domain optical coherence tomography (SD-OCT), Optovue iVue, on morphofunctional assessment of filtering blebs after different types of glaucoma surgery and point out the correlation between of morphologic features of blebs (bleb-wall thickness, scleral flap profile, and presence of hyporeflective spaces and internal cavity) and intraocular pressure (IOP). Methods: Thirty-eight eyes of thirty-two primarly open angle glaucoma patients, following three different types of glaucoma surgery (trabeculectomy with MMC 0.3%; with the implant of the Ex-PRESS device; with the insertion of Ologen [OLO]) were recruited. Patients attended a 6-month follow-up with intermediate checks at 1 week, 1 month and 3 months. Each visit include the evaluation of bleb using both slit lamp biomicroscopy and OCT. Results: In all patients, regardless of the type of surgery, a very significant reduction of IOP is observed after surgery. The bleb-wall thickness and the scleral flap profile are not shown to be sensitive parameters to identify the functionality of the bleb. The presence of hyporeflective spaces and of a cavity over the sclera is an important sign of bleb functionality. Among the different types of surgery, a higher percentage of blebs provided with hyporeflective spaces is in the Ex-PRESS group. In regards to the presence of a cavity over the sclera, there are no differences between the different groups. Comparing the blebs with filtering aspect at the OCT in the different groups, in the Ex-PRESS group there is a higher percentage of blebs with a filtering aspect compared to the other groups. Conclusions: Optovue iVue, is able to show detailed superficial features of the bleb which significantly correlate with the functionality of the bleb itself.

Relazione struttura/funzione e rapporto tra numero di cellule ganglionari retiniche e sensibilità luminosa differenziale espressa in scala logaritmica e lineare nel glaucoma

Le conte delle cellule ganglionari retiniche (RGC) peripapillari e maculari ottenute empiricamente discriminano bene tra i vari stadi di neuropatia ottica glaucomatosa. L’esame del campo visivo misura anche le sensibilita luminose differenziali (DLS) in decibel (dB), ma queste possono anche essere convertite in 1/Lambert (1/L). La correlazione del numero delle RGC con le sensibilita luminose differenziali mostra andamenti differenti a seconda della scala utilizzata: il ricorso a DLS espresse in 1/L dimostra l’assenza di una riserva funzionale e l’esistenza di una funzione continua e lineare, ma non migliora la correlazione struttura/funzione che e di tipo moderato. Focal e Global Loss Volume (FLV e GLV) hanno una buona accuratezza diagnostica nella neuropatia ottica glaucomatosa.

Utilizzo clinico di tomografia a coerenza ottica (OCT) e di polarimetria a scansione laser confocale (GDx-VCC) nel glaucoma

Lo scopo dello studio e stato di confrontare le misure di spessore dello strato delle fibre nervose (RNFL) valutate con polarimetria a scansione laser confocale (GDx-VCC) e tomografia a coerenza ottica (SD-OCT iVue) in pazienti con sospetta neuropatia ottica glaucomatosa. 34 pazienti consecutivi (68 occhi) sono stati sottoposti a valutazione specialistica e ad analisi morfometrica di RNFL con GDx-VCC e SD-OCT iVue. Le misure fornite dai due strumenti sono state correlate tra loro calcolando il coefficiente di correlazione R. La correlazione e statisticamente significativa anche se il grado di correlazione risulta modesto o moderato. Solo il 48 % degli esami risulta di qualita ottimale con entrambi gli strumenti (Q>7 o Scan Quality Index >50). L’uso di entrambi i metodi di analisi morfologica permette di avere l’ 85% di immagini di buona qualita e valutabili clinicamente da almeno uno strumento.

Relazione tra struttura e funzione del nervo ottico e stima delle cellule ganglionari retiniche nel glaucoma

Il glaucoma e una neuropatia ottica caratterizzata da perdita di cellule ganglionari retiniche (RGC) e fibre nervose da cui derivano alterazioni morfologiche del nervo ottico e difetti del campo visivo osservabili con la perimetria standard automatizzata (SAP). La diagnosi di un glaucoma iniziale puo tuttavia rivelarsi difficile sia facendo ricorso alla SAP che alla tomografia a coerenza ottica (OCT) capace di misurare lo spessore dello strato delle fibre nervose retiniche (RNFL) e del complesso delle cellule ganglionari (GCC). Recentemente Medeiros et al. hanno messo a punto una formula empirica che stima il numero di RGC presenti in base a dati ricavati sia da esami funzionali (SAP) e strutturali (OCT). Classificati i pazienti utilizzando il GSS2 di Brusini, abbiamo rilevato una correlazione molto buona tra i parametri funzionali considerati, anche se il Visual Field Index non identifica bene i primi segni di neuropatia. Risultato analogo si e riscontrato anche per gli algoritmi strutturali. Sebbene struttura e funzione correlino solo moderatamente tra loro, cio e senza dubbio interessante viste le profonde differenze tra SAP e OCT. La conta delle RGC peripapillari e maculari consentono un’ottimale distinzione tra i vari gruppi di pazienti appartenenti a stadi differenti di neuropatia e correlano inoltre molto bene coi parametri strutturali e funzionali.

Il color Doppler imaging nel glaucoma: confronto dello spettro Doppler dei vasi retrobulbari di un paziente glaucomatoso con uno sano

Si ritiene che le alterazioni della perfusione ematica dell’occhio abbiano un ruolo importante nel glaucoma primario ad angolo aperto. Per questo motivo l’esame CDI dei vasi retrobulbari viene usato a fini di ricerca per comprendere l’entita di queste alterazioni e il loro ruolo nella patogenesi della malattia. I parametri comunemente studiati sono il PSV, l’EDV e l’IR nell’arteria oftalmica, nell’arteria centrale della retina e nelle arterie ciliari posteriori brevi. Alla luce di un recente lavoro che ha trovato differenze statisticamente significative per i parametri ESA e Sm/Dm nell’arteria oftalmica, presentiamo i risultati dello studio CDI di un caso di glaucoma a pressione normale e lo confrontiamo con un controllo sano. Le misure ottenute concordano con la letteratura in quanto, fatta eccezione per il PSV dell’arteria oftalmica, notiamo velocita inferiori per tutti i parametri e in tutti i vasi, associati a un aumento dell’indice di resistivita. Inoltre, sempre concordemente alla letteratura, l’ESA risulta piu basso e l’Sm/Dm maggiore se confrontato con i valori misurati in un volontario sano. Ulteriori studi saranno necessari per comprendere l’entita delle alterazioni nel patologico e l’influenza che esse possono avere sulla progressione del danno al nervo ottico.